Expression analysis of the prostaglandin E2 production pathway in human pancreatic cancers

Objectives: There is strong evidence for an important role of cyclooxygenase (COX) 2 and COX-2-generated PGE(2) during pancreatic tumorigenesis. Cyclooxygenase 2 has therefore become a potential chemotherapeutic target for pancreatic cancer. However, recent studies raised concerns regarding the safety of selective COX-2 inhibitors. Although the benefits of COX-2 inhibition may eventually outweigh the associated cardiovascular risks, there are a number of alternative targets for inhibiting the formation of PGE(2) in human tumors that may prove less harmful to the patient. This study aimed at analyzing the expression of various proteins involved in the generation of PGE2 in human pancreatic cancers. Methods and Results: Real-time polymerase chain reaction and Western blot analyses demonstrated overexpression of cytoplasmic phospholipase A2, COX-2, cytoplasmic prostaglandin E synthase, and microsomal prostaglandin E synthases 1 and 2 in most human pancreatic cancers when compared with matched normal pancreas. Immunohistochemistry revealed expression of these proteins predominantly by pancreatic cancer cells. Variable expression of these proteins was also confirmed in several human pancreatic cancer cell lines. Conclusions: Our studies demonstrated for the first time that various proteins involved in the generation of PGE2 are overexpressed in human pancreatic cancers. These proteins may represent potentially novel targets for the therapy of pancreatic cancers.